Toxoplasmosis.pptx

What is toxoplasmosis? Toxoplasmosis is an infection caused by a single-celled parasite called Toxoplasma gondii. While the parasite is found throughout the world, more than 40 million people in the United States may be infected with the Toxoplasma parasite.

1. Toxoplasmosis 12/14/2016 Lecture Eight

2. Like most of the Apicomplexa, Toxoplasma is an obligate intracellular parasite.  Its life cycle includes two phases called the intestinal-enteric and Extraintestinal phases . Infects a wide range of animals, birds but does not appear to cause disease in them The intestinal phase occurs in cats only (wild as well as domesticated cats) and produces " oocysts ." The extraintestinal phase occurs in all infected animals produces " tachyzoites " and, eventually, " bradyzoites " or “tissue cysts.“   The disease toxoplasmosis can be transmitted by ingestion of oocysts (in cat feces) or bradyzoites (in raw or undercooked meat ). A disease of the blood and lymphatic system. Primary problem is a congenital infection of fetus, resulting in either a stillbirth or a child with severe brain damage or vision problems. 12/14/2016 Lecture Eight

3. 12/14/2016 Lecture Eight Transmission Eating undercooked, contaminated meat (especially pork, lamb, and venison). Accidental ingestion of undercooked, contaminated meat after handling it and not washing hands thoroughly ( Toxoplasma  cannot be absorbed through intact skin). Eating food that was contaminated by knives, utensils, cutting boards and other foods that have had contact with raw, contaminated meat. Drinking water contaminated with  Toxoplasma gondii .

4. 12/14/2016 Lecture Eight Accidentally swallowing the parasite through contact with cat feces that contain  Toxoplasma . This might happen by cleaning a cat's litter box when the cat has shed Toxoplasma  in its feces touching or ingesting anything that has come into contact with cat feces that contain  Toxoplasma accidentally ingesting contaminated soil (e.g., not washing hands after gardening or eating unwashed fruits or vegetables from a garden) Mother-to-child (congenital) transmission. Receiving an infected organ transplant or infected blood via transfusion, though this is rare.

5. Morphology 1. tachyzoites ( trophozoites ). 2. tissue cysts ( bradyzoites ). 3. oocyst. Oocyst Tachyzoites Bradyzoites Toxoplasma gondii exists in three forms : 12/14/2016 Lecture Eight

6. Morphologically different stages : Trophozoite : or Tachyzoite is crescent or banana shaped with a pointed end and a bluntly round end. In the acute stage of the disease, trophozoites are usually scattered in the blood, cerebrospinal fluid and various pathological exudates arranged in pairs or singly. The trophozoite community is within a host cell parasitophorous vacuole not surrounded by a cystic wall. Hence they are also known as a pseudocyst (usually a swelling macrophage with a several parasites). The trophozoites within a pseudocyst are Tachyzoites . 12/14/2016 Lecture Eight

7. Tissue cyst : is round and oval in appearance and the cystic wall created by the parasite is thin, but firm and elastic. The protozoa multiply in the tissue cyst slowly and repeatedly. The trophozoites in the cyst are called Bradyzoites , which are similar to the Tachyzoites , but smaller than them. 12/14/2016 Lecture Eight

8. Tissue cysts of Toxoplasma gondii filled with bradyzoites 12/14/2016 Lecture Eight As host resistance develops, usually around 3 weeks post infection, tissue cysts may form in many organs, primarily in brain and muscle

9. Schizont : can be found in the small intestinal mucosa of the infected cat. Schizonts contain about 4-40 merozoites . Gametocytes are also found in the small intestinal mucosa of the cat. Male gametocytes produce 12-32 male gametes, crescent in shape. The female gametocyte develops into a female gamete. Male and female gametes fertilize to form a zygote that develops into an oocyst . oocyst is round or elleptic and covered with a smooth transparent cystic wall consisting of two layers. Each mature oocyst contains two sporocysts with each sporocyst containing 4 sporozoites . 12/14/2016

10. Two different kinds of host are needed in the sexual and asexual generations present in the life cycle of T. gondii . Sexual development or Gametogony occurs in the epithelial cells of the small intestine of cats(intra-intestinal phase). The binary fission and endodyogeny ( process of internal budding in which two daughter cells are formed within the body of the mother cell that dies when the progeny are released) of the asexual development takes place in various nucleated cells outside the intestine of many spp. Of mammals and birds. 12/14/2016 Lecture Eight

11. Life Cycle The life cycle of the parasite consists of 3 stages as follows Tachyzoites , the multiplying that which invade and multiply within cells, Bradyzoites,the slowly multiplying inside tisssue cysts, seen during latent and chronic infection. (c)Sporozoites inside oocysts , which are shed in cat feces and remain in the environment. In cats, which are definitive hosts. both schizogony and gametogony takeplace in the epithelial cells of the small intestine ( enteric cycle). Cat is infected either by ingestion of oocyst shed in its faeces or by eating flesh of other animals or birds containing tissue cysts The oocysts produced by gametogony are shed in faeces . They develop into infective forms in soil or water. 12/14/2016 Lecture Eight

12. When ingested by other animals, birds or human. which are intermediate hosts. The oocysts release sporozoites which infect the intestinal epithelial cells. Here, they multiply by endodyogeny to form tachyzoites . The host cell ruptures releasing numerous trophozoites which spread through blood and lymph infecting any type of nucleated cell in various tissues and organs. This is known as the exoenteric cycle. Primary infection with the parasite may be asymptomatic, acute or chronic. In chronic infections tissue cysts are produced within muscles and other tissues. 12/14/2016 Lecture Eight

13. When other intermediate hosts ingest these tissue cysts, the asexual cycle is repeated. When cats ingest the tissue cysts they become infected and in them both asexual and sexual cycles are repeated Artificial methods of human infection are laboratory contamination, blood transfusion and organ transplantation. Congenital infection also occurs. When food or water contaminated with T.gondii oocyst or animal body containing cysts, pseudocyst ingested by a feline, sporozoites , bradyoites or Tachyzoites are released in the small intestine. These parasites invade the epithelial cells. 12/14/2016 Lecture Eight

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16. Pathogenesis The Tacyzoites have predilection for parenchymal cells and Reticulo endothelial system and directly destroys the cells. Humans are relatively resistant to infection But low grade infection of lymph node persists When tissue cysts ruptures – releases number of Bradyzoites Local hypersensitivity reaction may cause inflammation. Causes blocking of blood vessels Causes death of cells near damaged area 12/14/2016 Lecture Eight

17. Clinical Features Most human infections are asymptomatic. Clinical toxoplasmosis may be congenital or acquired. Congenital Toxoplasmosis Congenital toxoplasmosis results when infection is transmitted transplacentally from mother to fetus. The risk of fetal infection rises with the progress of gestation, from 25 per cent when the mother acquires primary infection in the first trimester, to 65 per cent in the third trimester. Conversely the severity of foetal damage is highest when infection is transmitted in early pregnancy. Mothers with chronic or latent Toxoplasma infection acquired earlier do not ordinarily infect their babies, but in some women with latent or chronic infection may be to babies. 12/14/2016 Lecture Eight

18. the tissue cyst may be reactivated during pregnancy and liberate trophozoites which may reach the fetus in utero . Most infected newborns are asymptomatic at birth and may remain so throughout. Some develop clinical manifestations of toxoplasmosis weeks, months or even years after birth. The manifestations may be chorioretinitis , strabismus, blindness, deafness, epilepsy or mental retardation. A few are born with manifestations of acute toxoplasmosis, which may include fever, jaundice, diarrhoea , hydrocephalus, microcephaly,cerebralcalcifications,cataract,glaucoma,chorioretinitis, optic atrophy, lymphadenitis, pneumonitis, myocarditis and hepatosplenomegaly . 12/14/2016 Lecture Eight

19. Acquired Toxoplasmosis Infection acquired postnatally is mostly asymptomatic. The most common manifestation of acute acquired toxoplasmosis is lymphadenopathy, Fever, headache, myalgia and splenomegaly. The illness may resemble mild ‘flu’ or infectious mononucleosis lymphadenopathy may persist. In some there may be a typhus- like,with pneumonitis, myocarditis and meningoencephalitis , which may be fatal. Another type of toxoplasmosis is ocular . Approximately 35 per cent of cases of chorioretinitis . Toxoplasmosis primarily involving the central nervous system is usually fatal and often found in AIDS, severely in the immunodeficient , brain involvement is common. Host defense against Toxoplasma infection involves both humoral and cellular responses. Specific IgG antibody can lyse extracellular trophozoites . But activated T cells and natural killer cells appear to be more important in containing the infection and preventing clinical disease. 12/14/2016 Lecture Eight

20. Congenital Toxoplasmosis Intracerebral calcification. Chorioretinitis . Ocular toxoplasmosis Hydrocephaly. Microcephaly . Convulsions. Mental retardation . Cardiomegaly . toxoplasmic encephalitis Congenital disease

21. Congenital toxoplasmosis is a problem in 1-5/1000 pregnancies If a woman is infected for the first time during pregnancy the parasite can cross the placenta and cause fetal disease. Both the* probability and severity of the disease depend on when the infection takes place during pregnancy. Early : low transmission, but severe disease Late : high transmission, more benign symptoms. Hydrocephaly. * Intracerebral calcification .

22. Diagnosis Laboratory diagnosis may be made by microscopic demonstration of the parasite, by its isolation or by serological tests. Giemsa stained impression smears of lymphnodes , bone marrow, spleen or brain may occasionally show the trophozoites , which can be readily identified by their morphology. Inoculation of tissue culture and animal : T. gondii can also be isolated by inoculation of tissue, also can be isolated by intraperitoneal inoculation of body fluids or ground tissues into young laboratory mice that are free from infection. If no death occurs, the mice are observed for about six weeks ,and tail or heart blood is then tested for specific antibody. The diagnosis is confirmed by demonstration of tissue cysts in the brain of inoculated mice. Polymerase chain reaction : Toxoplasmal DNA can be detected in the specimens by PCR. 12/14/2016 Lecture Eight

23. 12/14/2016 Lecture Eight Skin test results showing delayed skin hypersensitivity to Toxoplasma gondii antigens. Serology : Sabin –Feldman dye test:   This test depends upon the appearance in 2-3 weeks of antibodies that render the membrane of laboratory –cultured living T. gondii impermeable to alkaline methylen blue, so that organisms are unstained in the presence of positive serum. It is one of the first methods used to diagnose toxoplasmosis. This highly sensitive and specific test is a complement – mediated neutralizing antigen –antibody reaction. It is performed in reference laboratories.   2- Latex agglutination test:   It is a simple test. It shows 94 % agreement with the dye test. The latex particles are coated with inactivated T. gondii soluble antigen. This test does not require heat inactivation of serum samples.

24. 12/14/2016 Lecture Eight 3 – Other tests : The most common method of laboratory diagnosis is by serology. Several serological tests are available. Indirect immunofluorescence, indirect haemagglutination , complement fixation , ELISA. The standard test used now is ELISA, separately for IgM and IgG antibodies. The presence of IgM antibody in the absence of IgG denotes current infection, IgM antibody with high titre IgG suggests infection in the recent past; Negative IgM with positive IgG indicates past infection. This is subject to individual variation. In some cases IgM antibody may persist up to 18 months. Serial ELISA provides better information than a single test . Diagnosis of congenital toxoplasmosis can be established by: •PCR : PCR of the amniotic fluid to detect the B1 gene of the parasite. •Serology : The presence of IgM ( which dose not cross the placenta ) in the infant̕s circulation is diagnostic but often this is not found . Specific IgG in the infant̕s circulation may be maternal origin or due to infection. Testing of infant̕s blood at 2 monthly intervals will show whether the IgG antibody level is decreasing . At 6- 10 months the infant̕s circulation should not contain maternal IgG and therefore persistence of IgG beyond this time is indicative of infection in the infant.

25. Amniocentesis Done around 16 th week of pregnancy A long needle is inserted into the Amniotic sac and amniotic fluid is drawn.

26. Treatment Combination of Pyramethamine and Sulphadiazine or Trisulfapyramidines Other alternative Drugs Spiramycin Clindamycin Trimethoprim – Sulphmethoxazole In pregnancy – Spriamycin is recommended drug 12/14/2016 Lecture Eight

27. Control of Toxoplasmosis Avoidance of human contact with Cat feces is highly important measure. Changing of Cat litter and safe disposal can prevent transmission Pregnant women should avoid contact with kittens 12/14/2016 Lecture Eight

28. Screening of pregnant women Periodic screening of pregnant women with high risk for IgG and IgM antibodies to Toxoplasmosis is recommended 12/14/2016 Lecture Eight Care of the Meat Avoid eating raw or undercooked meat. Freezing < -20 c Heating at 50 c for 4-6 minutes destroys the cysts and sterilizes the meat.